Download Elastic Properties and Composition of the Aortic Wall in Old

Elastic Properties and Composition of the Aortic Wall in
Old Spontaneously Hypertensive Rats
Valérie Marque, Pascal Kieffer, Jeffrey Atkinson, Isabelle Lartaud-Idjouadiene,
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Abstract—We hypothesized that age-linked changes in the composition and elastic properties of the arterial wall occur
earlier in hypertensive than in normotensive rats. We evaluated the consequences of hypertension and aging on aortic
mechanics, geometry, and composition in 3-, 9-, and 15-month-old awake Wistar-Kyoto rats (WKY) (normotensive) and
spontaneously hypertensive rats (SHR) (hypertensive). The elastic modulus of the thoracic aorta, calculated from aortic
pulse wave velocity and geometry, was higher in young and adult SHR than in age-matched WKY, as was wall stress;
however, isobaric pulse wave velocity and pulse wave velocity–pressure curves were similar. Elastic modulus, isobaric
pulse wave velocity, and the slope of the pulse wave velocity–pressure curve dramatically increased in old SHR
compared with age-matched WKY; there was no further elevation of blood pressure or wall thickness. Fibrosis did not
develop with age in SHR, and the ratio of elastin to collagen decreased in a similar fashion with aging in both strains.
In conclusion, although elastic properties of the aortic wall are not intrinsically modified in young and adult SHR in
comparison to age-matched WKY, aging is associated with a dramatic stiffening of the aortic wall in old SHR but not
in WKY. Changes in blood pressure, aortic wall geometry, or scleroprotein composition do not appear to explain this
age-linked aortic stiffening in SHR, suggesting that other mechanisms of disorganization of the media may be involved.
(Hypertension. 1999;34:415-422.)
Key Words: elastin n collagen n elasticity n stress n aging n hypertension, experimental
A
ging produces many vascular changes, one of the most
important being a progressive rise in arterial stiffness.1,2
The thickness of the media increases with age because of
smooth muscle cell hypertrophy and fibrosis. The elastic fiber
network develops longitudinal fissures, transverse breaks,
and fragmentation. Such structural modifications (fibrosis
and degradation of elastin) lead to a decrease in elasticity.3
Hypertension also may produce an increase in large-artery
stiffness,4,5 at least when elastic properties are measured at a
hypertensive level.6 –9
However, previous experiments on the effects of hypertension were performed mainly in young or adult subjects,6 –9
and the consequences of a combination of hypertension and
aging on the elastic properties of the aortic wall remain
unexplored.10,11 The first objective of the present study was to
evaluate the elastic properties of the aorta of 3-, 9-, and
15-month-old normotensive Wistar-Kyoto rats (WKY) and
hypertensive spontaneously hypertensive rats (SHR). This
was done by analyzing in awake animals the relationships
between (1) pulse wave velocity and central mean aortic
blood pressure under a wide range of pressure and (2) elastic
modulus and circumferential wall stress. We hypothesized
that age-linked mechanical alterations of the arterial wall will
occur earlier in SHR than in normotensive rats. Our second
objective was to study possible links between elastic proper-
ties and the geometry and scleroprotein composition of the
vessel wall.
Methods
Animals
Two-month-old normotensive WKY (n530) and SHR (n530) were
purchased from Iffa Credo (L’Arbresle, France), kept under standard
conditions (2161C°, lights on 6 AM to 6 PM), and given a standard
rodent diet (UAR) and water ad libitum until 3, 9, or 15 months of
age. Experiments were performed in accordance with the guidelines
of the European Union and the French Ministry of Agriculture.
Aortic Pulse Wave Velocity in Awake Rats
Procedures have been described in detail elsewhere.12,13 Briefly,
polyethylene cannulas (0.96/0.58 mm OD/ID) were chronically
implanted under halothane (2%)/oxygen anesthesia into the descending thoracic aorta, the abdominal aorta, and the abdominal vena cava.
There were no deaths during the period of recovery from surgery (24
hours), and weight loss was 561% in both SHR and WKY.
Twenty-four hours later, the aortic cannulas of nonanesthetized,
unrestrained rats were connected to the pressure recording system,
for which the dynamic frequency response is flat with a phase lag
,26° up to 30 Hz and then slightly underdamped.13 The pressure
signals were converted into digital form and recorded online at a
sampling rate of 256 Hz. After a 30-minute habituation period,
baseline parameters were determined beat to beat and averaged over
periods of 4 seconds every 30 seconds for 30 minutes. An algorithm
detected the maximal and minimal values of each pressure signal,
Received December 8, 1998; first decision December 18, 1998; revision accepted May 17, 1999.
From the Laboratoire de Pharmacologie Cardiovasculaire, Faculté de Pharmacie, Université Henri Poincaré-Nancy 1, Nancy, France.
Correspondence to Jeffrey Atkinson, Laboratoire de Pharmacologie Cardiovasculaire, Faculté de Pharmacie, Université Henri Poincaré-Nancy 1, 5 rue
Albert Lebrun, 54000 Nancy, France. E-mail [email protected]
© 1999 American Heart Association, Inc.
Hypertension is available at http://www.hypertensionaha.org
415
416
Hypertension
September 1999
calculated mean aortic blood pressure (mm Hg) from the waveform
area, pulse pressure as the diastolic-systolic difference, and heart rate
(bpm) by counting the entire number of cycles over the 4-second
period.
Pulse wave velocity (cm/s) was calculated as the distance between
the 2 cannula tips (measured in situ after postmortem fixation by
placing a damp cotton thread onto the aorta) divided by the transit
time. Transit times (ms) were measured online by an algorithm that
systematically shifted in time the peripheral pressure waveform with
respect to the central pressure waveform and determined the value of
the time shift giving the highest correlation.12,13 The accuracy of
transit time determination was improved by performing the calculation for the entire waveform, with the use of least squares analysis of
the differences in amplitude between the central and peripheral
signals, and by increasing the number of sampling points by creating
intermediate points for the peripheral signal by linear interpolation.
Because the sampling rate was 1/3.9 ms and 10 intermediate points
were created, the theoretical resolution of the calculated transit time
was 0.39 ms, which gives a 63.9% error for the lowest value of
transit time observed in the present study for 15-month-old SHR (9.9 ms).
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Pulse Wave Velocity–Pressure Curves During
Pharmacological Hypotension in Awake Rats
After baseline hemodynamic measurements, central mean aortic
blood pressure was reduced in a stepwise fashion (10 mm Hg per
step) to half its initial value by progressively increasing the
infusion rate of a sodium nitroprusside solution (Sigma Chemical
Company; 2.3 mmol/L in phosphate buffer 10 mmol/L, pH 7.4, at
25°C).12 At each stabilized pressure step, 15 measurements of
aortic blood pressure and transit time were performed and
averaged. At the end of infusion, animals had received a volume
,4% of their total blood volume; mean dose of sodium nitroprusside was 140614 nmol/kg per minute in 3-month-old rats
(PAge,0.05) versus 100618 nmol/kg per minute in 9-month-old
rats and 9569 nmol/kg per minute in 15-month-old rats
(PStrain50.2121, PAge3Strain50.2864; 2-way ANOVA). For each rat,
pulse wave velocity was expressed as a function of central mean
aortic blood pressure with the use of an exponential model14
[pulse wave velocity5b z ea(central mean aortic blood pressure)]. Slopes (a) and
intercepts (b) were treated as independent, parametric variables
and averaged. Because heart rate, via a change in the harmonic
composition of the pressure pulse, influences pulse wave velocity,15 and baroreflex function may be different between groups,
we also studied the “heart rate– corrected” pulse wave velocity–
pressure curves by dividing pulse wave velocity by heart rate
recorded simultaneously at each pressure step.
Descending Thoracic Aorta Geometry, Wall Stress,
and Elastic Modulus
At the end of the hemodynamic measurements, rats were killed with
a sodium pentobarbital overdose and perfused for 30 minutes at their
baseline central mean aortic blood pressure with 10% formol
containing phosphate-buffered saline. A 0.5-cm sample of the
proximal descending thoracic aorta was excised, immersed in 10%
formol, then dehydrated in graded ethanol solutions and embedded in
paraffin. Three 20-mm-thick sections were stained with hematoxylineosin for measurement of internal diameter and medial thickness
(Saisam, Microvision Instruments). The coefficient of variation for 3
repeated measurements of medial thickness/internal diameter performed by one observer was ,4.5%; the interobserver coefficient of
variation for the same measurements was ,3.5%.
Elastic modulus and wall stress (106 dyne/cm2) were calculated
from the Moens-Korteweg or Lamé equations: elastic
modulus5(PWV2 z Di z r)/h and wall stress5(CMABP z Di)/2h,
where PWV is baseline pulse wave velocity in awake rats (cm/s), Di
is internal diameter (cm), h is medial thickness (cm), r is blood
density (1.05 g/cm3), and CMABP is baseline central mean aortic
blood pressure in awake rat (dyne/cm2). For each group, elastic
modulus was plotted against wall stress with an exponential model
[elastic modulus5b z ea(wall stress)].
Descending Thoracic Aortic Wall Composition
A second 0.5-cm sample of the thoracic aorta was hydrolyzed in
hydrochloric acid (6 mol/L, 24 hours, at 105°C). Protein content was
determined by the dinitrofluorobenzene reaction,16 with 92 used for
the molecular weight of an amino acid.17 Collagen content was
determined by the chloramine T and paradimethylaminobenzaldehyde reaction as (hydroxyproline content37.46/protein content)3100.17 Desmosine and isodesmosine contents (cross-linking
amino acids specific to elastin) were determined by capillary zone
electrophoresis,18 and elastin content was calculated as (desmosine
plus isodesmosine3200/protein content)3100.19,20 The ratio of elastin to collagen was also calculated.
A third 1-cm sample of the thoracic aorta was excised, and the
wall calcium content was determined by atomic absorption spectrophotometry (AA10, Varian Ltd) after mineralization and nitric acid
digestion.21
Statistical Analysis
Values are given as mean6SEM. Differences between groups
(P,0.05) were evaluated with 2-way ANOVA (factors: age and
strain) plus the Bonferroni test. In the cases in which this analysis
revealed a significant interaction between the age and strain sources
of variation, the effect of age was evaluated with a 1-way ANOVA
performed for each strain separately.
Results
Body Weight, Central Aortic Blood Pressure, and
Heart Rate in Awake Rats
There were no significant differences in body weight between
WKY and SHR at 3, 9, and 15 months of age (Table 1). In
both strains, there was rapid growth during maturation
followed by slower growth with aging. Central diastolic,
mean, pulse, and systolic aortic blood pressures were higher
in SHR than in age-matched WKY. Maturation and aging
were associated with a slight decrease in central diastolic and
mean aortic blood pressures, which were similar in both
strains. The decrease in systolic and pulse pressures during
maturation and aging was higher in SHR than in WKY. Heart
rate was slightly higher in SHR than in age-matched WKY
and rose slightly with maturation and aging in both strains.
Baseline Pulse Wave Velocity and Pulse Wave
Velocity–Pressure Curves in Awake Rats
Baseline pulse wave velocity was higher in SHR than in
age-matched WKY (Table 1). Effects of maturation and aging
were different in the 2 strains. Pulse wave velocity decreased
slightly with maturation in SHR, then rose to a very high level
in 15-month-old SHR. There were no changes in baseline
pulse wave velocity with maturation or aging in WKY.
At 3 and 9 months of age, the pulse wave velocity–pressure
curves of SHR were similar to those of WKY (Figure 1a),
indicating that aortic elasticity was similar in both strains at a
given level of aortic blood pressure. However, at 15 months
of age, the pulse wave velocity–pressure curve was steeper in
SHR than in WKY. After correction of pulse wave velocity
by heart rate, similar results were obtained, with a steeper
curve in 15-month-old SHR (Figure 1b).
Thoracic Descending Aorta Geometry, Wall Stress,
and Elastic Modulus
Internal thoracic aorta diameter and medial thickness were
higher in SHR than in age-matched WKY (Table 2). Geom-
Marque et al
Aortic Elasticity in Old Hypertensive Rats
417
TABLE 1. Body Weight, Baseline Central Aortic Blood Pressures, Heart Rate, and Pulse Wave
Velocity in Awake 3-, 9-, and 15-Month-Old Hypertensive and Normotensive Rats
Parameter/Age, mo
SHR
WKY
PAge
PStrain
PAge3 Strain
0.0001
0.7357
0.1248
0.0008
0.0001
0.5095
0.0001
0.0001
0.2311
0.0001
0.0001
0.0414
0.0011
0.0001
0.0024
0.0065
0.002
0.6856
0.0342
0.0001
0.0261
Body weight, g
3
31865 (n58)
30966 (n511)
9
415615 (n510)
39466 (n59)
15
441612 (n513)
464611 (n511)
Diastolic pressure, mm Hg
3
14162
10862
9
13164
10161
15
12264
9663
3
17263
12762
9
15965
12362
15
14765
11563
3
20763
14763
9
18866
14563
15
17466*
13563*
3
6662
4061
9
5862*
4462
15
5262*
3961
Mean pressure, mm Hg
Systolic pressure, mm Hg
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Pulse pressure, mm Hg
Heart rate, bpm
3
36767
32868
9
403610
365615
15
392611
371617
3
764646
545641
9
663637
541625
15
888650†
537635
Pulse wave velocity, cm/s
*P,0.05 vs 3 months of age in the same strain, 1-way ANOVA.
†P,0.05 vs 9 months of age in the same strain; 1-way ANOVA.
etry did not significantly change with maturation, but internal
diameter and medial thickness increased with aging in both SHR
and WKY. Thickening of the aortic wall was directly related to
age-associated dilation as medial thickness/internal diameter
remained constant with age in both strains, with a higher value
in SHR than in age-matched WKY. The linear relationship
between medial thickness and internal diameter was similar in
WKY and SHR at all 3 ages (intercept50.02860.007 mm,
slope50.02460.005, n530, P50.0001 in 3-, 9-, and 15-monthold WKY; intercept50.04060.014 mm, slope50.02860.008,
n530, P50.0022 in 3-, 9-, and 15-month-old SHR).
Wall stress was higher in 3- and 9-month-old SHR than in
age-matched WKY (Table 2). As medial thickness/internal
diameter remained constant but central mean aortic pressure
decreased with aging in both strains, wall stress decreased
with aging in both SHR and WKY. At 15 months of age, wall
stress was similar in SHR and WKY.
Elastic modulus was higher in SHR than in age-matched
WKY (Table 2). It did not significantly change with maturation but dramatically increased with aging in SHR. There
were no changes in elastic modulus with maturation or aging
in WKY. Elastic modulus was significantly related to wall
stress in all groups (Figure 2). The ratio of elastic modulus to
wall stress was clearly higher in 15-month-old SHR than in
younger groups, whereas there was no difference between
SHR and WKY rats at 3 and 9 months of age (Table 2).
Thoracic Descending Aorta Composition
Globally, the evolution with age of the composition of the aortic
wall was similar in both strains, because the “age3strain”
interaction was not significant for any of the components (Table
3). Protein as well as elastin contents were similar in SHR and in
age-matched WKY and decreased in a similar fashion with
maturation and aging in both strains. The collagen content was
lower in SHR than in age-matched WKY and did not change
markedly with age. Consequently, the ratio of elastin to collagen,
which was higher in SHR than in age-matched WKY, decreased
in a similar fashion with maturation and aging in both strains.
Finally, the evolution of total calcium content with maturation
and aging was similar in both groups.
418
Hypertension
September 1999
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Figure 1. Pulse wave velocity–pressure curves (a)
and heart rate– corrected pulse wave velocity–
pressure curves (b) (average of the individual
exponential relationships y5b z ea z x obtained during sodium nitroprusside infusion) in 3-, 9-, and
15-month-old WKY (M) and SHR (f). *P,0.05 vs
age-matched WKY. Slopes, intercepts, and probability values are shown.
Discussion
The aims of the present study were to determine whether aortic
stiffening occurs earlier in SHR than in WKY during aging and
to analyze the relationship between aortic wall structure and
mechanics at different ages. The main findings are that aortic
stiffness is not increased in young and adult SHR compared with
age-matched WKY when determined under isobaric conditions,
but stiffness is dramatically increased with aging in SHR despite
no substantial increase in blood pressure or changes in aortic
geometry and scleroprotein composition.
The aortic wall is stiffer in young and adult SHR than in
their normotensive counterparts when determined at their
individual blood pressures. This increase in aortic stiffness is
directly related to the higher pressure and wall stress levels,
with elastic modulus strongly correlated to wall stress in SHR
(and WKY) at 3 and 9 months of age and the ratio of elastic
modulus to wall stress similar in both strains. Furthermore,
when measured at a given level of blood pressure, pulse wave
velocities of 3- and 9-month-old SHR are similar to those of
age-matched WKY: pulse wave velocity–pressure curves
Marque et al
Aortic Elasticity in Old Hypertensive Rats
419
TABLE 2. Thoracic Aortic Wall Geometry, Wall Stress, and Elastic Modulus in 3-,
9-, and 15-Month-Old Hypertensive and Normotensive Rats
SHR
WKY
PAge
PStrain
PAge3Strain
3
1.6160.07
1.3260.05
0.0286
0.0001
0.9197
9
1.5560.06
1.3360.05
1.7860.10
1.4960.08
3
8166
5662
0.0019
0.0001
0.3618
9
8064
6263
15
9564
6763
3
0.05160.004
0.04360.001
0.4117
0.0008
0.6278
9
0.05260.002
0.04760.002
0.05460.003
0.04560.002
3
2.360.2
2.060.1
0.0011
0.0054
0.4329
9
2.160.1
1.760.1
1.960.1
1.760.1
3
1262
761
0.0403
0.0001
0.0588
9
961
761
15
1662†
761
3
5.160.4
3.860.6
0.0013
0.0003
0.0105
9
4.560.5
3.860.3
15
8.860.9*†
4.160.4
Parameter/Age, mo
Internal diameter, mm
15
3
Medial thickness, 10 mm
Medial thickness/internal diameter
15
6
2
Wall stress, 10 dyne/cm
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15
6
Elastic modulus, 10 dyne/cm
2
Elastic modulus/wall stress
*P,0.05 vs 3 months of age in the same strain, 1-way ANOVA.
†P,0.05 vs 9 months of age in the same strain, 1-way ANOVA.
obtained in SHR overlap those of WKY at both ages. This
indicates that aortic stiffness is not intrinsically increased in
3- and 9-month-old SHR, confirming previous studies on
large-artery distensibility performed in young or adult hypertensive subjects and SHR.3– 6,22 The later study22 reported
similar aortic distensibility in SHR and WKY after ultrasonic
measurements, a method that allows dynamic evaluation of
the aortic elastic properties. Interestingly, dynamic distensibility and compliance may be maintained in hypertensive rats
because enlargement of the artery compensates for a stiffer
wall (with stiffening measured under static conditions and
enlargement measured under unstressed conditions, ie, at a
low pressure value).23 In the present study, elasticity has been
evaluated under static conditions by stepwise decreases in
aortic mean blood pressure and pulse wave velocity. Pulse
wave velocity and the Moens-Korteweg elastic modulus
reflect directly the elastic properties of the arterial wall
material. All these observations lead to the conclusion that
elastic properties of the aortic wall may be maintained in
young and adult SHR not only under dynamic22 but also
under static (present results) conditions of measurement. This
conclusion should be tempered, however, by the fact that
unstressed volume was not evaluated in the present study, and
elastic modulus was calculated from both in vivo and in vitro
measurements.
In contrast to the results in young rats, pulse wave velocity
and elastic modulus are dramatically increased in old SHR
compared with age-matched WKY. Furthermore, the pulse
wave velocity–pressure curve is shifted upward with a steeper
slope, and the ratio of elastic modulus to wall stress is
markedly higher in old SHR. This indicates that aging
intrinsically modifies the aortic elastic properties in SHR,
earlier than in normotensive WKY. In another normotensive
rat model, aging increases passive circumferential and longitudinal stiffness from 23 months of age, with different
modulation of the biaxial stiffness by smooth muscle activation.24 In the present study, circumferential and longitudinal
stiffness cannot be distinguished because pulse wave velocity
measurement reflects both of these components; the latter, as
well as the lack of unstressed volume measurement (see
above), tempers our interpretations. Whatever these limitations, the strong increase in ratio of elastic modulus to wall
stress clearly reflects an age-related stiffening of the aortic
wall in SHR. This aortic stiffening cannot be related to wall
thickening because the medial thickness/internal diameter
ratio remained constant with age in both strains.
Therefore, other determinants of the aortic wall elastic
properties (eg, relative proportion and/or interaction between
smooth muscle cells and extracellular matrix) may change
420
Hypertension
September 1999
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Figure 2. Elastic modulus (EM) as a function of wall stress (WS)
(y5b z ea z x) in 3-, 9-, and 15-month-old WKY (M) and SHR (f).
Slopes, intercepts, and probability values are shown.
during aging in hypertensive rats. The increase in medial
thickness with aging, with no parallel changes in protein,
collagen, or elastin contents, suggests a greater proportion of
smooth muscle cells in the aortic wall of SHR, but this would
tend to maintain aortic elastic properties at a low level, as it
does in young and adult SHR.5 Concerning the extracellular
matrix components, changes in collagen content are not
involved in the age-linked aortic stiffening in SHR, because
fibrosis does not develop with aging in SHR (or in WKY).
Second, even though the elastin content slightly decreases
with age, it does not decrease faster in SHR than in WKY,
and the ratio of elastin to collagen decreases in a similar
fashion with aging in both strains. Therefore, our results
exclude the possibility that changes in blood pressure, aortic
wall thickening, or modifications in scleroprotein content
play a major role in age-linked aortic stiffening observed in
SHR. One explanation may be that, despite the lack of change
in scleroprotein content, the degree of recruitment of stiff
collagen fibers is higher in old SHR because of the higher
internal diameter and wall stress. However, such a hypothesis
is weakened by the observation that age-induced enlargement
of the aorta is proportionally similar in both SHR and WKY
(111% between young and old rats).
Another possibility is that structural disorganization of
the media leads to mechanical alteration of the aortic wall
in old SHR. It has been shown recently that the elastin
network plays a major role in the maintenance of aortic
elastic properties in adult SHR, not through variations of
its total amount but through increases of the extent of its
anchorage to the smooth muscle cells.5,6 Similarly, an
increase in the fibronectin and integrin contents, through
changes in cell-matrix interactions, may participate in the
mechanical adaptation of the arterial wall to the higher
level of circumferential wall stress.22 It could be hypothesized that aging either amplifies such mechanical adaptation in SHR—a further increase in the number of
cell-matrix attachments leading finally to an increase in the
passive stiffness of the wall material— or reverses it. It
would be therefore interesting to repeat the type of
experiment of Bezie et al6,22 in old SHR.
Other hypotheses can also be advanced to explain the
age-linked aortic stiffening in SHR: a more rapid increase
with age in the ratio of collagen type I to III,25 an
accelerated accumulation of advanced glycation end products on both elastin and collagen fibers,26 or a change in
the elastic properties of the elastic lamellae themselves
after fragmentation induced by the cumulative fatiguing
cyclic stress.27 Finally, the fact that doses of sodium
nitroprusside required to modify pulse wave velocity
decrease with age, suggesting an increase in sensitivity of
the soluble guanylate cyclase, may be an indirect indication of a loss of the endothelium-dependent reduction in
vasomotor tone. This could account for the increased
arterial stiffness with age, because vascular smooth muscle
tone modulates arterial wall anisotropy differently with
aging.24 However, the latter conclusion was drawn on the
basis of experiments on the carotid artery, a more muscular
artery than the thoracic aorta; in the latter, changes in local
smooth muscle tone do not seem to modify markedly aortic
wall elasticity.12,28
Surprisingly, despite the dramatic age-linked aortic stiffening of the aortic wall, central systolic and pulse aortic
pressures are not increased but significantly decreased in old
SHR compared with other groups. This suggests that stroke
volume falls with aging in SHR. Old SHR have been
described as a good model of cardiac failure with reduced
ejection fraction,29 and the dramatic age-dependent aortic
stiffening observed in this strain may account for such a
cardiac dysfunction.
In conclusion, aortic stiffness is not intrinsically increased
in young or adult SHR, confirming previous studies of
large-artery distensibility. However, aging in SHR is associated with a dramatic stiffening of the aortic wall, which
cannot be explained by further increase in blood pressure or
substantial age-linked aortic wall thickening, fibrosis, or
elastocalcinosis. This suggests that some other structural
disorganization of the media (which occurs earlier in hypertensive than in normotensive rats, eg, changes in the number
Marque et al
Aortic Elasticity in Old Hypertensive Rats
421
TABLE 3. Thoracic Aortic Wall Contents of Total Protein, Collagen, Elastin, and
Calcium in 3-, 9-, and 15-Month-Old Hypertensive and Normotensive Rats
Parameter/Age, mo
SHR
WKY
PAge
PStrain
PAge3Strain
0.0003
0.1889
0.9614
0.0374
0.0001
0.6313
0.0004
0.2976
0.6609
0.0001
0.0001
0.8097
0.0072
0.6663
0.2364
Total protein, mg/g wet wt
3
26165
272610
9
28766
29364
15
25367
261610
3
3161
3862
9
3461
4262
15
3461
4462
3
6264
5664
9
5464
5164
15
4464
4463
3
1.8860.10
1.4660.06
9
1.6260.10
1.2260.09
15
1.3260.13
1.0260.08
Collagen, % of protein content
Elastin, % of protein content
Elastin/collagen content
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Calcium, mmol/g wet wt
3
761
862
9
1263
1363
15
961
561
of muscle to elastic lamellae connections, an increase in the
ratio of collagen type I to III, or an accumulation of the
advanced glycation end products) leads to mechanical alteration of the aortic wall in old SHR.
Acknowledgments
This study was supported by grants from the French Education and
Research Ministry (Paris, France); the Regional Development Committee (Metz, France); the Greater Nancy Urban Council (Nancy,
France); and Rhône Poulenc-Rorer (Paris, France). The authors
thank Drs René Peslin, Claude Duvivier, and Philippe Giummelly
(Institut National de la Santé et de la Recherche Médicale U14 and
Laboratoire de Pharmacologie Cardiovasculaire, Faculté de Pharmacie, Nancy, France) for help with signal analysis and Dr Nathalie
Dartois (Rhône Poulenc-Rorer, Paris, France) for her intellectual,
material, and moral support.
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Downloaded from http://hyper.ahajournals.org/ by guest on June 18, 2017
Elastic Properties and Composition of the Aortic Wall in Old Spontaneously Hypertensive
Rats
Valérie Marque, Pascal Kieffer, Jeffrey Atkinson and Isabelle Lartaud-Idjouadiene
Downloaded from http://hyper.ahajournals.org/ by guest on June 18, 2017
Hypertension. 1999;34:415-422
doi: 10.1161/01.HYP.34.3.415
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